Trifluoroacetic acid → HCID 25177157, compound

Participants

Reaction Steps

5-(2-Amino-6-{2-[2-(2-aminoethoxy)ethylcarbamoyl]ethylsulfanyl}pyrimidin-4-yl)-2,4-dimethylbenzoic acid tert-butyl ester (78 mg, 0.159 mmol) obtained in Step 1 above was dissolved in dichloromethane (3 ml), and then trifluoroacetic acid (1 ml) was added thereto. After this solution was stirred at room temperature for two hours, the solvent was distilled off under reduced pressure. The resulting crude product was dissolved in a mixed solvent of N,N-dimethylformamide (25 ml) and tetrahydrofuran (75 ml), and then 1-hydroxybenzotriazole (134 mg, 0.795 mmol), diisopropylethylamine (137 μl, 0.795 mmol), and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (152 mg, 2.2 mmol) were sequentially added thereto. After the solution was stirred at room temperature for 16 hours, 1-hydroxybenzotriazole (270 mg, 1.59 mmol), diisopropylethylamine (274 μl, 1.59 mmol), and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (304 mg, 1.59 mmol) were added thereto. After the solution was stirred at 50° C. for seven hours, the solvent was distilled off under reduced pressure. The residue was diluted with ethyl acetate. The ethyl acetate solution was washed with a saturated aqueous sodium bicarbonate solution (twice), and dried over anhydrous sodium sulfate. After the inorganic salt was removed by filtration, the filtrate was concentrated. The resulting residue was purified by preparative thin layer silica gel chromatography (developing solvent: dichloromethane:methanol=15:1). The obtained crude product was washed with dichloromethane to yield 4-amino-20,22-dimethyl-14-oxa-7-thia-3,5,11,17-tetraazatricyclo[17.3.1.12,6]tetracosa-1(22),2(24),3,5,19(23),20-hexaene-10,18-dione (Compound 29) (2 mg) as a white solid material.

Provenance & Evidence